HEPATITIS E The Leading Cause of Acute Viral Hepatitis in the World The hepatitis E virus is the leading cause of acute (short-lived) viral hepatitis in the world, and occurs primarily in Africa, Central Asia and Mexico. It accounts for half of all acute hepatitis infection outbreaks in children and adults in areas where it is endemic. Worldwide, hepatitis E virus (HEV) infection is more prevalent than hepatitis A virus infection. Researchers suspect that as many as 20 percent of the world’s population has been infected by the hepatitis E virus. The virus is most common in people between the ages of 15 to 40. In young children, HEV infection often has no symptoms. In adult populations, hepatitis E can wreak havoc. Since the early 1950s, there have been water-borne hepatitis E epidemics reported in New Delhi, India, the former Soviet Union, Nepal, Myanmar (Burma), Algeria, Pakistan, Cote d’Ivoire (Ivory Coast), Bor- neo and in refugee camps in Sudan and Somalia. The virus is transmitted through food or water contaminated by the feces of infected people, but unlike the hepatitis A virus, it is not spread through close person-to-person contact. For some reason that eludes Like hepatitis A, an HEV infection never develops medical researchers, between into a chronic or long-term illness. However, in 15 to 25 percent of pregnant adults, hepatitis E is more severe than hepatitis A, women infected with hepatitis E die, according to the National with death rates reaching between 1 and 2 percent. Centers for Disease Control In contrast, adult death rates from hepatitis A are and Prevention (CDC). less than 0.4 percent. Its symptoms are similar to other types of viral hepatitis, including malaise, anorexia, abdominal pain, jaundice and fever. The acute stage of the disease can last less than two weeks. While symptoms are nonexistent in children and mild in most adults, in pregnant women this infection can be deadly. Like hepatitis A, there is no treatment for an HEV infection. No vaccine has been developed that prevents HEV infection. PKIDs’ PHR 197 Identification of the Hepatitis E Virus In 1955, a large epidemic of acute hepatitis swept through New Delhi, India, affecting 29,000 people after raw sewage contaminated the city’s drinking water. At the time, health officials assumed it was an outbreak of hepatitis A. In the early 1990s, scientists tested blood samples that had been drawn and then stored from some of the patients stricken during the New Delhi epidemic. They found a new infectious viral agent that they called enteric (relating to the gut or intestine) non-A, non-B hepatitis. In a retrospective study conducted in the early 1990s, scientists were able to identify the molecular components of this viral agent and it became known as hepatitis E. The “E” was chosen to illustrate its enteric, endemic and epidemic qualities that capture the epidemiology of this virus. “E” also made sense alphabetically, because hepatitis A, B, C and D viruses had already been identified as causing hepatitis (liver inflammation) in humans. Hepatitis E, like hepatitis C, is a positive-strand RNA (ribonucleic acid) virus that appears to be a unique agent, and has not been conclusively identified as belonging to any known virus family, though it does share characteristics with the Calicivirus family. The International Committee on the Taxonomy of Viruses placed the hepatitis E virus in a separate family called hepatitis E-like viruses. Analysis of the virus’s RNA shows that the virus forms a genetically distinct group that is closer to a rubella virus than to members of the Caliciviridae family. When it enters a cell, the virus’s genetic material is inserted into the infected cell and “progeny” viruses are then produced by the infected cell. Most replication of the hepatitis E virus ultimately occurs in the liver, and virus particles are present in the bile and feces of the infected person from late incubation of the virus to the first week of illness. The incubation period of the virus in humans ranges from three to nine weeks. Patients who show symptoms develop typical acute hepatitis symptoms, such as nausea, anorexia, fever, upper abdominal pain, cola-colored urine and jaundice—yellow coloring of the skin and whites of the eyes. However, the disease can also be silent, with no symptoms at all, which is common in children. 198 PKIDs’ PHR HEPATITIS E In two human volunteer studies, liver enzyme elevations, which occur when the liver is irritated and liver cells are damaged or die, occurred four to five weeks after oral ingestion of the virus and persisted for 20 to 90 days. During an acute infection, there can also be elevated levels of bilirubin (bile pigments) in the blood and urine, and a mild increase in the alkaline phosphatase, a bile duct enzyme. In the study, virus excretion in human stool occurred about four weeks after ingestion of the virus and persisted for about two weeks. Only 1 to 2 percent of non-pregnant patients infected with HEV experience serious or fatal liver disease symptoms. The disease usually resolves itself within two weeks. It is not clear whether infection with this virus confers any life-long immunity against future infections, as is the case with hepatitis A virus infections. Hepatitis E in Patients with Existing Hepatitis In the case of hepatitis A—the other viral hepatitis spread by infected feces—there is potentially a worsening or sudden onset of liver disease among people who contract hepatitis A if they already have chronic hepatitis B or C virus infections. However, there has been little research performed to date to determine to what degree HEV infection accelerates or worsens liver damage in people with chronic hepatitis B or C. In a letter to The New England Journal of Medicine, Dr. Eduardo Bruno Martins of the Federal University of Rio de Janeiro in Brazil reported finding coinfection with hepatitis E and C in 11 percent of 50 adult patients with documented fulminant (life-threatening) hepatitis. He suggests hepatitis E may play a role in causing life-threatening hepatitis in patients with chronic hepatitis C virus infections. However, to date there is no detailed evidence that HEV infection increases the severity of liver disease in adults or children who already have chronic viral hepatitis. Epidemiology of Hepatitis E Historically, researchers thought widespread infection of HEV was found only in India, Central Asia, parts of Africa and in Mexico. According to CDC, currently 40 percent of acute viral hepatitis infections in India result from HEV infection. The largest recorded outbreak of hepatitis E occurred in Xinjing, China in 1986-88 with more than 119,000 documented cases. PKIDs’ PHR 199 In India, 70 percent of HEV infections occur in children. A study by the Department of Pediatric Gastroenterology at the S.M.S. Medical College in Jaipur found 70 percent of pediatric HEV infections were caused by contaminated drinking water and 20 percent by contaminated food. They suggest 9.5 percent resulted from house- hold contact, which is inconsistent with CDC’s HEV is transmitted primarily through report that this is not a disease transmitted food and water contaminated by feces through person-to-person or household contact. from HEV-infected people. Indian researchers reported a few cases of According to the CDC, there is little mother-to-child (vertical) transmission if the evidence of transmission through mother had hepatitis E during the third trimester person-to-person or close household of pregnancy. contact. Hepatitis E viruses were also found in breast milk, but there are no known documented cases of breast milk transmitting the virus to infants. Among blood donors worldwide, CDC has reported that 11 to 25 percent from develop- ing countries test positive for HEV antibodies. Scientists cannot confirm that infection with HEV confers life-long immunity against re-infection. Therefore, molecular medicine researchers suggest people may be re-infected over the course of their lives, and can continually contribute infected feces to areas without clean drinking water and with substandard waste-water treatment facilities. Scientists also wonder whether as-yet unidentified strains or variants of hepatitis E viruses can cause re-infections in developing countries. Hepatitis E Prevalence in the United States According to CDC, virtually all cases of acute hepatitis E in the United States have occurred among travelers returning from countries where hepatitis E is endemic, such as India. However, tests on healthy blood donors in the United States show that between 1 and 5 percent have HEV antibodies in their blood. Most of those with antibodies are from urban areas. The high HEV antibody rate has puzzled CDC researchers. Some suggest the high prevalence of antibodies in the absence of disease and symptoms is due to infection with 200 PKIDs’ PHR HEPATITIS E a viral strain of hepatitis E that doesn’t cause disease, according to Dr. Robert H. Purcell, chief of the hepatitis division in the National Institute of Allergy and Infectious Diseases’ (NIAID) Laboratory of Infectious Diseases. He also suggests that animals may be acting as reservoirs of HEV and passing a weak- ened form of the virus on to humans. Non-Human Reservoirs of Hepatitis E Viruses A study led by researchers at the National Institutes of Health (NIH) suggests that hepatitis E viruses are common among wild rats in the United States. Given the unexpected 1 to 5 percent rate of blood donors in the United States with hepatitis E antibodies, researchers are now examining any potential connection between animals and HEV infection in humans. Scientists analyzed blood samples from 239 rats captured in alleyways in Baltimore, along the Mississippi River levee in New Orleans and in urban and rural areas of Hawaii.